1. Field of the Invention
The present invention relates to a method for separating particles or components of a fluid. The invention has particular advantages in connection with separating blood components, such as white blood cells and platelets.
This application is related to U.S. Pat. No. 5,722,926, issued Mar. 3, 1998; U.S. Pat. No. 5,951,877, issued Sep. 14, 1999; U.S. patent application Ser. No. 08/853,374, filed May 8, 1997 (pending); and U.S. patent application Ser. No. 09/270,105, filed Mar. 16, 1999 (pending). The entire disclosure of each of these U.S. patents and patent applications is incorporated herein by reference.
2. Description of the Related Art
In many different fields, liquids carrying particle substances must be filtered or processed to obtain either a purified liquid or purified particle end product. In its broadest sense, a filter is any device capable of removing or separating particles from a substance. Thus, the term xe2x80x9cfilterxe2x80x9d as used herein is not limited to a porous media material but includes many different types of devices and processes where particles are either separated from one another or from liquid.
In the medical field, it is often necessary to filter blood. Whole blood consists of various liquid components and particle components. Sometimes, the particle components are referred to as xe2x80x9cformed elementsxe2x80x9d. The liquid portion of blood is largely made up of plasma, and the particle components include red blood cells (erythrocytes), white blood cells (i.e., leukocytes), and platelets (thrombocytes). While these constituents have similar densities, their average density relationship, in order of decreasing density, is as follows: red blood cells, white blood cells, platelets, and plasma. In addition, the particle constituents are related according to size, in order of decreasing size, as follows: white blood cells, red blood cells, and platelets. Most current purification devices rely on density and size differences or surface chemistry characteristics to separate and/or filter the blood components.
Numerous therapeutic treatments require groups of particles to be removed from whole blood before liquid and/or particle components can be infused into a patient. For example, cancer patients often require platelet transfusions after undergoing ablative, chemical, or radiation therapy. In this procedure, donated whole blood is processed to remove platelets and these platelets are then infused into the patient. However, if a patient receives an excessive number of foreign white blood cells as contamination in a platelet transfusion, the patient""s body may reject the platelet transfusion, leading to a host of serious health risks.
Typically, donated platelets are separated or harvested from other blood components using a centrifuge. The centrifuge rotates a blood reservoir to separate components within the reservoir using centrifugal force. In use, blood enters the reservoir while it is rotating at a very rapid speed and centrifugal force stratifies the blood components, so that particular components may be separately removed. Centrifuges are effective at separating platelets from whole blood, however they typically are unable to separate all of the white blood cells from the platelets. Historically, blood separation and centrifugation devices are often unable to consistently (99% of the time) produce platelet product that meets the xe2x80x9cleukopoorxe2x80x9d standard of less than 5xc3x97106 white blood cells for at least 3xc3x971011 platelets collected.
Because typical centrifuge platelet collection processes are unable to consistently and satisfactorily separate white blood cells from platelets, other processes have been added to improve results. In one procedure, after centrifuging, platelets are passed through a porous woven or non-woven media filter, which may have a modified surface, to remove white blood cells. However, use of the porous filter introduces its own set of problems. Conventional porous filters may be inefficient because they may permanently remove or trap approximately 5-20% of the platelets. These conventional filters may also reduce xe2x80x9cplatelet viability,xe2x80x9d meaning that once passed through a filter a percentage of the platelets cease to function properly and may be partially or fully activated. In addition, porous filters may cause the release of brandykinin, which may lead to hypotensive episodes in a patient. Porous filters are also expensive and often require additional time consuming manual labor to perform a filtration process.
Although porous filters are effective in removing a substantial number of white blood cells, they have drawbacks. For example, after centrifuging and before porous filtering, a period of time must pass to give activated platelets time to transform to a deactivated state. Otherwise, the activated platelets are likely to clog the filter. Therefore, the use of at least some porous filters is not feasible in on-line processes.
Another separation process is one known as centrifugal elutriation. This process separates cells suspended in a liquid medium without the use of a membrane filter. In one common form of elutriation, a cell batch is introduced into a flow of liquid elutriation buffer. This liquid which carries the cell batch in suspension, is then introduced into a funnel-shaped chamber located on a spinning centrifuge. As additional liquid buffer solution flows through the chamber, the liquid sweeps smaller sized, slower-sedimenting cells toward an elutriation boundary within the chamber, while larger, faster-sedimenting cells migrate to an area of the chamber having the greatest centrifugal force.
When the centrifugal force and force generated by the fluid flow are balanced, the fluid flow is increased to force slower-sedimenting cells from an exit port in the chamber, while faster-sedimenting cells are retained in the chamber. If fluid flow through the chamber is increased, progressively larger, faster-sedimenting cells may be removed from the chamber.
Thus, centrifugal elutriation separates particles having different sedimentation velocities. Stoke""s law describes sedimentation velocity (SV) of a spherical particle as follows:   SV  =            2      9        ⁢                            r          2                ⁢                  (                                    ρ              p                        -                          ρ              m                                )                ⁢        g            η      
where, r is the radius of the particle, xcfx81p is the density of the particle, xcfx81m is the density of the liquid medium, xcex7 is the viscosity of the medium, and g is the gravitational or centrifugal acceleration. Because the radius of a particle is raised to the second power in the Stoke""s equation and the density of the particle is not, the size of a cell, rather than its density, greatly influences its sedimentation rate. This explains why larger particles generally remain in a chamber during centrifugal elutriation, while smaller particles are released, if the particles have similar densities.
As described in U.S. Pat. No. 3,825,175 to Sartory, centrifugal elutriation has a number of limitations. In most of these processes, particles must be introduced within a flow of fluid medium in separate discontinuous batches to allow for sufficient particle separation. Thus, some elutriation processes only permit separation in particle batches and require an additional fluid medium to transport particles. In addition, flow forces must be precisely balanced against centrifugal force to allow for proper particle segregation.
Further, a Coriolis jetting effect takes place when particles flow into an elutriation chamber from a high centrifugal field toward a lower centrifugal field. The fluid and particles turbulently collide with an inner wall of the chamber facing the rotational direction of the centrifuge. This phenomenon mixes particles within the chamber and reduces the effectiveness of the separation process. Further, Coriolis jetting shunts flow along the inner wall from the inlet directly to the outlet. Thus, particles pass around the elutriative field to contaminate the end product.
Particle mixing by particle density inversion is an additional problem encountered in some prior elutriation processes. Fluid flowing within the elutriation chamber has a decreasing velocity as it flows in the centripetal direction from an entrance port toward an increased cross-sectional portion of the chamber. Because particles tend to concentrate within a flowing liquid in areas of lower flow velocity, rather than in areas of high flow velocity, the particles concentrate near the increased cross-sectional area of the chamber. Correspondingly, since flow velocity is greatest adjacent the entrance port, the particle concentration is reduced in this area. Density inversion of particles takes place when the centrifugal force urges the particles from the high particle concentration at the portion of increased cross-section toward the entrance port. This particle turnover reduces the effectiveness of particle separation by elutriation.
For these and other reasons, there is a need to improve particle separation and/or separation of components of a fluid.
The present invention is directed to a method that substantially obviates one or more of the limitations and disadvantages of the related art. To achieve these and other advantages and in accordance with the purpose of the invention, as embodied and broadly described herein, the invention includes a particle separation method. In the method, a fluid chamber is rotated about an axis of rotation. At least liquid, first particles, and second particles are flowed into the fluid chamber via an inlet of the fluid chamber. At least some of the first particles are retained in the fluid chamber while liquid and at least some of the second particles are permitted to flow from the fluid chamber via an outlet of the fluid chamber. During the process, direction of flow in the fluid chamber is reversed such that liquid and at least some of the retained first particles pass from the fluid chamber via the inlet.
In an aspect of the invention, the reversing of flow direction includes flowing liquid into the fluid chamber via the outlet. For example, the liquid flowed through the outlet is obtained by initially separating a substance into its liquid and particle components.
In another aspect, the first particles, the second particles, and/or the liquid include(s) blood components. In one preferred practice of the present invention, the first particles include white blood cells, the second particles include platelets, and the liquid includes plasma.
There are many different ways in which the first particles could be retained in the fluid chamber. In one aspect, the method includes forming in the fluid chamber a saturated fluidized particle bed including at least the second particles, and this bed obstructs passage of at least some of the first particles. In another aspect, at least some of the first and second particles are separated in the fluid chamber by elutriation.
In a further aspect, the invention includes a method of separating components of a fluid. In the method, a separation vessel is rotated about the axis of rotation along with the fluid chamber. Fluid is passed into the separation vessel and separated into at least a relatively high density component, relatively intermediate density components including at least first and second subcomponents, and a relatively low density component. At least a portion of the relatively intermediate density components are removed from the separation vessel and flowed into the fluid chamber. At least some of the first subcomponent is retained in the fluid chamber and at least some of the second subcomponent is permitted to flow from an outlet of the fluid chamber. During the separation procedure, flow in the fluid chamber is reversed to pass at least some of the retained first subcomponent from the fluid chamber to the separation vessel.
In one preferred aspect, the fluid includes blood components and the reversing of flow direction occurs when a predetermined amount of fluid is passed into the separation vessel.
In another aspect, at least some of the low density component is removed from the separation vessel, and the reversing of flow direction includes passing the removed low density component into the fluid chamber via the outlet of the fluid chamber.
In yet another aspect, an interface is formed in the separation vessel between the intermediate density components and the relatively high density component, and the position of the interface in the separation vessel is adjusted so that the interface is positioned closer to a port providing flow communication between the separation vessel and the fluid chamber. Preferably, a dam extends in the separation vessel and the interface is adjusted to a position closer than a portion of the dam to the axis of rotation such that the interface and the dam define a pocket for the first subcomponent passed from the fluid chamber during the reversing of flow direction.
There are many different types of fluid chambers and separation vessels that could be used to practice the present invention. There are also many different ways in which particles and/or components could be separated in these structures. In the preferred practice of the invention, the separation vessel includes a barrier configured to accumulate particular particles and/or components, and the fluid chamber has an interior configured to permit formation therein of a saturated fluidized particle bed and/or an elutriation field.
It is to be understood that both the foregoing general description and the following detailed description are exemplary, and are intended to provide further explanation of the invention as claimed.